Can the Sunshine Vitamin Improve Mood and Self-Management in Women with Diabetes? Diabetes affects 1 in 10 persons in the United States and is projected to increase to 1 in 4 persons by 2050. Women with type 2 diabetes have worse outcomes than men with type 2 diabetes. This may be due to depression which affects over 25% of women with diabetes. Depression interferes with self-care behaviors and significantly impacts glycemic control. Antidepressants are effective for the treatment of depression but can disrupt glycemic control and cause weight gain, making diabetes self-management challenging. Research has shown that vitamin D supplementation can improve depressive symptoms in healthy, obese individuals suggesting its use for amelioration of these symptoms in other groups. We recently completed a six month proof of concept study using a one group, pre-post test design to examine the effects of weekly vitamin D supplementation (50,000 IUs weekly) in women with type 2 diabetes who had significant depressive symptoms (a score > 16 on the Center for Epidemiologic Studies Depression Tool (CES-D) (NIH 5P60DK020595, pilot project). We found a significant decrease in depression symptoms, improvements in diabetes self- management, and a decrease in systolic blood pressure. Several small studies have shown that vitamin D supplementation may lower blood pressure by direct and indirect vascular effects. We now propose a randomized trial to determine the efficacy of vitamin D3 supplementation on depressive symptoms, self- management, and blood pressure in women with type 2 diabetes who have significant depressive symptoms (n=150). Using a stratified block randomization (strata based on depression symptom severity) women will be assigned to either weekly vitamin D3 supplementation (50,000 IUs) or a matching weekly placebo for a period of six months. Since guidelines recommend assessing vitamin D levels at three months upon initiating this dose, study measurements will be collected at baseline, three, and six months. The following outcomes will be measured: depressive symptoms, diabetes self-management (self-efficacy, diabetes distress, diabetes self- care behaviors), and systolic blood pressure. We hypothesize that women receiving vitamin D3 supplementation will report fewer depressive symptoms, increased diabetes self- management mediated by depression improvement, and have a lower systolic BP compared to those taking placebo. We will also explore a possible mechanistic effect of vitamin D supplementation on depression. Evidence indicates that in depression, pro-inflammatory biomarkers, notably cytokines and C-reactive protein (CRP), are elevated. Some of these inflammatory biomarkers alter the metabolic pathway of tryptophan by shunting it away from serotonin synthesis via stimulation of the enzyme indoleamine 2, 3-dioxygenase (IDO). Several studies (not depression studies) have reported that Vitamin D can decrease levels of inflammatory biomarkers. Thus we will explore whether vitamin D supplementation decreases inflammatory biomarkers (CRP, interleukin-6, and tumor necrosis factor- ) providing evidence for a plausible mechanism of antidepressant activity. Vitamin D supplementation has minimal side effects and is low in cost. Thus, the potential for using this therapy is highly significant fr women with type 2 diabetes and other chronic populations who suffer from symptoms of depression which significantly impacts the self-management of their health.